Anemia is frequently observed in the elderly. We have shown that in most, the cause is not obvious and that anemic elderly have significantly lower leukocyte counts than non-anemic elderly. Additional information suggests that anemic aged have reduced numbers of marrow myeloid precursors and the number of myeloid committed stem cells (CFU-C) are less than non-anemic aged or young subjects. This proposal aims at extending these preliminary observations. Erythroid precursors/kg body weight will be measured by ferrokinetics. Myeloid and megakaryocytic precursors will be quantitated from the ratio: erythroid precursors in sections of marrow biopsy and erythroid mass. Erythroid and myeloid progenitor cells will be quantitated in vitro cell culture and from cell ratios in smears of marrow aspirates. Basal studies will evaluate hematopoiesis in young and old males and females who are hematologically normal. These values will be compared to measures in aged subjects with the anemia of senescence. Additional studies aimed at delineating the cause of anemia will also be undertaken. An intrinsic cell deficiency will be evaluated by quantitating erythroid precursors. End organ failure will be examined by culturing at varying concentrations of erythropoietin. The interrelationship between hematocrit and circulating erythropoietin will also be determined. In addition to these studies the effect of age on the ability of the marrow to respond to stress will be examined in mice. The various studies proposed will shed insight into the pathophysiologic effects of age on hematopoiesis. Preliminary data, if confirmed, may suggest that reduced reserve is not a universal feature of the aging process. The presence of an as yet to be defined pathologic mechanism may exist in these subjects. These studies will provide the foundation for the future evaluation of the mechanisms involved in the effects of age on marrow function.